# Targeted Therapy in Hepatobiliary Pancreatic Cancer (HPC): Advantages and Advancements of Antibody Drug Conjugates, a Type of Chemo-Biologic Hybrid Drugs

**Authors:** Tushar Deb Nath, Attrayo Mukherjee, Subhash C. Chauhan, Debasish Bandyopadhyay

PMC · DOI: 10.3390/ijms27062707 · 2026-03-16

## TL;DR

This review explores how antibody-drug conjugates (ADCs) offer a promising targeted therapy for hepatobiliary pancreatic cancer by delivering chemotherapy directly to cancer cells.

## Contribution

The paper provides a comprehensive overview of ADCs in HPC, highlighting their mechanisms, clinical trials, and future directions to improve efficacy.

## Key findings

- ADCs show potential to increase survival and reduce side effects in HPC patients.
- Challenges include targeting specific antigens like B7-H3, c-MET, and Trop-2.
- Future improvements involve addressing tumor heterogeneity and resistance.

## Abstract

Currently, there are very few efficient treatment options for hepatobiliary pancreatic cancer (HPC), which comprises pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC), and hepatocellular carcinoma (HCC). The HPC tumors are the most lethal malignant tumors in the world. Traditional chemotherapy offers little survival benefit and is associated with notable systemic toxicity, which has made antibody–drug conjugates (ADCs) a hopeful treatment option. Strong cytotoxic drugs combine with monoclonal antibodies to attack tumor-associated antigens. This review discusses the benefits and current developments of Antibody–Drug Conjugates (ADCs) in treating HPC. It also covers their mechanisms of action, ongoing clinical trials, and the challenges of targeting specific antigens like B7-H3, c-MET, and Trop-2. ADCs deliver chemotherapy directly to cancer cells while protecting healthy tissues. It also addresses the favorable outcomes of several preclinical and clinical studies and highlights future paths to enhance ADC efficacy, including addressing tumor heterogeneity, overcoming resistance, and optimizing drug-delivery techniques. This approach has the possibility to further increase patient survival and minimize side effects in HPC patients. To the best of our knowledge and based on the available literature, we have made every effort to include all relevant publications; any inadvertent omissions are entirely unintentional.

## Linked entities

- **Proteins:** CD276 (CD276 molecule), MET (MET proto-oncogene, receptor tyrosine kinase), TACSTD2 (tumor associated calcium signal transducer 2)
- **Diseases:** pancreatic ductal adenocarcinoma (MONDO:0005184), biliary tract cancer (MONDO:0003060), hepatocellular carcinoma (MONDO:0007256)

## Full-text entities

- **Genes:** TACSTD2 (tumor associated calcium signal transducer 2) [NCBI Gene 4070] {aka EGP-1, EGP1, GA733-1, GA7331, GP50, M1S1}, CD276 (CD276 molecule) [NCBI Gene 80381] {aka 4Ig-B7-H3, B7-H3, B7H3, B7RP-2}, MET (MET proto-oncogene, receptor tyrosine kinase) [NCBI Gene 4233] {aka AUTS9, DA11, DFNB97, HGFR, RCCP2, c-Met}
- **Diseases:** PDAC (MESH:D021441), BTC (MESH:D001661), HPC (MESH:D010190), HCC (MESH:D006528), toxicity (MESH:D064420), cancer (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13027249/full.md

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Source: https://tomesphere.com/paper/PMC13027249